First Author | Yu FX | Year | 2013 |
Journal | Genes Dev | Volume | 27 |
Issue | 11 | Pages | 1223-32 |
PubMed ID | 23752589 | Mgi Jnum | J:199172 |
Mgi Id | MGI:5500980 | Doi | 10.1101/gad.219402.113 |
Citation | Yu FX, et al. (2013) Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation. Genes Dev 27(11):1223-32 |
abstractText | The Hippo tumor suppressor pathway plays an important role in tissue homeostasis that ensures development of functional organs at proper size. The YAP transcription coactivator is a major effector of the Hippo pathway and is phosphorylated and inactivated by the Hippo pathway kinases Lats1/2. It has recently been shown that YAP activity is regulated by G-protein-coupled receptor signaling. Here we demonstrate that cyclic adenosine monophosphate (cAMP), a second messenger downstream from Galphas-coupled receptors, acts through protein kinase A (PKA) and Rho GTPases to stimulate Lats kinases and YAP phosphorylation. We also show that inactivation of YAP is crucial for PKA-induced adipogenesis. In addition, PKA activation in Drosophila inhibits the expression of Yorki (Yki, a YAP ortholog) target genes involved in cell proliferation and death. Taken together, our study demonstrates that Hippo-YAP is a key signaling branch of cAMP and PKA and reveals new insight into mechanisms of PKA in regulating a broad range of cellular functions. |